tbuckley/cabot-search huggingface dataset:
Congenital aniridia beyond black eyes: From phenotype and novel genetic mechanisms to innovative therapeutic approaches
Authors: Alejandra Daruich, Melinda Duncan, Matthieu P. Robert, Neil Lagali, Elena V. Semina, Daniel Aberdam, Stefano Ferrari, Vito Romano, Cyril Burin des Roziers, Rabia Benkortebi, Nathalie De Vergnes, Michel Polak, Frederic Chiambaretta, Ken K. Nischal, Francine Behar-Cohen, Sophie Valleix, Dominique Bremond-Gignac
Journal: Progress in Retinal and Eye Research (2022)

Congenital PAX6-aniridia, initially characterized by the absence of the iris, has progressively been shown to be associated with other developmental ocular abnormalities and systemic features making congenital aniridia a complex syndromic disorder rather than a simple isolated disease of the iris. Moreover, foveal hypoplasia is now recognized as a more frequent feature than complete iris hypoplasia and a major visual prognosis determinant, reversing the classical clinical picture of this disease. Conversely, iris malformation is also a feature of various anterior segment dysgenesis disorders caused by PAX6-related developmental genes, adding a level of genetic complexity for accurate molecular diagnosis of aniridia. Therefore, the clinical recognition and differential genetic diagnosis of PAX6-related aniridia has been revealed to be much more challenging than initially thought, and still remains under-investigated. Here, we update specific clinical features of aniridia, with emphasis on their genotype correlations, as well as provide new knowledge regarding the PAX6 gene and its mutational spectrum, and highlight the beneficial utility of clinically implementing targeted Next-Generation Sequencing combined with Whole-Genome Sequencing to increase the genetic diagnostic yield of aniridia. We also present new molecular mechanisms underlying aniridia and aniridia-like phenotypes. Finally, we discuss the appropriate medical and surgical management of aniridic eyes, as well as innovative therapeutic options. Altogether, these combined clinical-genetic approaches will help to accelerate time to diagnosis, provide better determination of the disease prognosis and management, and confirm eligibility for future clinical trials or genetic-specific therapies.
Combination Therapy With Immunomodulators Improves the Pharmacokinetics of Infliximab But Not Vedolizumab or Ustekinumab
Authors: Andres J. Yarur, Dermot McGovern, Maria T. Abreu, Adam Cheifetz, Konstantinos Papamichail, Parakkal Deepak, Alexandra Bruss, Poonam Beniwal-Patel, Marla Dubinsky, Stephan R. Targan, Gil Y. Melmed
Journal: Clinical Gastroenterology and Hepatology (2022)
Routine Molecular Profiling in Both Resectable and Unresectable Pancreatic Adenocarcinoma: Relevance of Cytologic Samples
Authors: Miriam Redegalli, Greta Grassini, Gilda Magliacane, Lorenza Pecciarini, Marco Schiavo Lena, Chanel E. Smart, Rebecca L. Johnston, Nicola Waddell, Roberta Maestro, Marina Macchini, Giulia Orsi, Maria Chiara Petrone, Gemma Rossi, Gianpaolo Balzano, Massimo Falconi, Paolo G. Arcidiacono, Michele Reni, Claudio Doglioni, Maria Giulia Cangi
Journal: Clinical Gastroenterology and Hepatology (2022)
Pan American League of Associations for Rheumatology guidelines for the treatment of giant cell arteritis
Authors: Marina Scolnik, Maria L Brance, Daniel G Fernández-Ávila, Emilia Inoue Sato, Alexandre W S de Souza, Sebastián J Magri, Lina M Saldarriaga-Rivera, Manuel F Ugarte-Gil, Luis F Flores-Suarez, Alejandra Babini, Natalia V Zamora, María L Acosta Felquer, Facundo Vergara, Leandro Carlevaris, Santiago Scarafia, Enrique R Soriano Guppy, Sebastian Unizony
Journal: The Lancet Rheumatology (2022)
Lupus low disease activity state and remission and risk of mortality in patients with systemic lupus erythematosus: a prospective, multinational, longitudinal cohort study
Authors: Rangi Kandane-Rathnayake, Vera Golder, Worawit Louthrenoo, Yi-Hsing Chen, Jiacai Cho, Aisha Lateef, Laniyati Hamijoyo, Shue-Fen Luo, Yeong-Jian J Wu, Sandra V Navarra, Leonid Zamora, Zhanguo Li, Sargunan Sockalingam, Yasuhiro Katsumata, Masayoshi Harigai, Yanjie Hao, Zhuoli Zhang, B M D B Basnayake, Madelynn Chan, Jun Kikuchi, Tsutomu Takeuchi, Sang-Cheol Bae, Shereen Oon, Sean O'Neill, Fiona Goldblatt, Kristine Pek Ling Ng, Annie Law, Nicola Tugnet, Sunil Kumar, Cherica Tee, Michael Tee, Naoaki Ohkubo, Yoshiya Tanaka, DaeYoung Yu, Chetan S Karyekar, Chak Sing Lau, Julie A Monk, Mandana Nikpour, Alberta Hoi, Eric F Morand
Journal: The Lancet Rheumatology (2022)
Click chemistry and drug delivery: A bird's-eye view
Authors: Shameer M. Kondengadan, Shubham Bansal, Ce Yang, Dongning Liu, Zach Fultz, Binghe Wang
Journal: Acta Pharmaceutica Sinica B (2022)

Click chemistry has been proven to be very useful in drug delivery. Due to the availability of a large number of click reactions with a various characteristics, selection of appropriate chemistry for a given application is often not a trivial task. This review is written for pharmaceutical researchers who are interested in click chemistry applications and yet may not be click chemistry experts. For this, the review gives an overview of available click reactions organized by application types. Further, the general understanding of click reactions being fast and high yielding sometimes overshadows the need to analyze reaction kinetics in assessing suitability of a given reaction for certain applications. For this, we highlight the need to analyze the relationship among reaction kinetics, concentration effects, and reaction time scales, knowing that lack of such analysis could easily lead to failures. Further, possible issues such as chemical stability with various click reagents are also discussed to aid experimental designs. Recent examples and extensive references are also provided to aid in-depth understanding of technical details. We hope this review will help those interested in using click chemistry in drug delivery to select the appropriate reactions/reagents and minimize the number of pitfalls.
Potential mechanisms underlying the accelerated cognitive decline in people with chronic low back pain: A scoping review
Authors: Zhixing Zhou, Edward S. Hui, Georg S. Kranz, Jeremy R. Chang, Katie de Luca, Sabina M. Pinto, Winnie WY Chan, Suk-yu Yau, Bolton KH Chau, Dino Samartzis, Mark P. Jensen, Arnold Y.L. Wong
Journal: Ageing Research Reviews (2022)

A growing body of evidence has shown that people with chronic low back pain (CLBP) demonstrate significantly greater declines in multiple cognitive domains than people who do not have CLBP. Given the high prevalence of CLBP in the ever-growing aging population that may be more vulnerable to cognitive decline, it is important to understand the mechanisms underlying the accelerated cognitive decline observed in this population, so that proper preventive or treatment approaches can be developed and implemented. The current scoping review summarizes what is known regarding the potential mechanisms underlying suboptimal cognitive performance and cognitive decline in people with CLBP and discusses future research directions. Five potential mechanisms were identified based on the findings from 34 included studies: (1) altered activity in the cortex and neural networks; (2) grey matter atrophy; (3) microglial activation and neuroinflammation; (4) comorbidities associated with CLBP; and (5) gut microbiota dysbiosis. Future studies should deepen the understanding of mechanisms underlying this association so that proper prevention and treatment strategies can be developed.
Hyper-CVAD and sequential blinatumomab for newly diagnosed Philadelphia chromosome-negative B-cell acute lymphocytic leukaemia: a single-arm, single-centre, phase 2 trial
Authors: Elias Jabbour, Nicholas J Short, Nitin Jain, Philip A Thompson, Tapan M Kadia, Alessandra Ferrajoli, Xuelin Huang, Musa Yilmaz, Yesid Alvarado, Keyur P Patel, Guillermo Garcia-Manero, Walid Macaron, Rebecca Garris, Marina Konopleva, Farhad Ravandi, Hagop Kantarjian
Journal: The Lancet Haematology (2022)
Transbronchial needle aspiration combined with cryobiopsy in the diagnosis of mediastinal diseases: a multicentre, open-label, randomised trial
Authors: Ye Fan, An-Mei Zhang, Xian-Li Wu, Zan-Sheng Huang, Konstantina Kontogianni, Kai Sun, Wan-Lei Fu, Na Wu, Wolfgang M Kuebler, Felix J F Herth
Journal: The Lancet Respiratory Medicine (2022)
SIRT6 Mitigates Heart Failure With Preserved Ejection Fraction in Diabetes
Authors: Xiaoqian Wu, Huan Liu, Alan Brooks, Suowen Xu, Jinque Luo, Rebbeca Steiner, Deanne M. Mickelsen, Christine S. Moravec, Jeffrey D. Alexis, Eric M. Small, Zheng Gen Jin
Journal: Circulation Research (2022)

Heart failure with preserved ejection fraction (HFpEF) is a growing health problem without effective therapies. Epidemiological studies indicate that diabetes is a strong risk factor for HFpEF, and about 45% of patients with HFpEF are suffering from diabetes, yet the underlying mechanisms remain elusive.Using a combination of echocardiography, hemodynamics, RNA-sequencing, molecular biology, in vitro and in vivo approaches, we investigated the roles of SIRT6 (sirtuin 6) in regulation of endothelial fatty acid (FA) transport and HFpEF in diabetes.We first observed that endothelial SIRT6 expression was markedly diminished in cardiac tissues from heart failure patients with diabetes. We then established an experimental mouse model of HFpEF in diabetes induced by a combination of the long-term high-fat diet feeding and a low-dose streptozocin challenge. We also generated a unique humanized SIRT6 transgenic mouse model, in which a single copy of human SIRT6 transgene was engineered at mouse Rosa26 locus and conditionally induced with the Cre-loxP technology. We found that genetically restoring endothelial SIRT6 expression in the diabetic mice ameliorated diastolic dysfunction concurrently with decreased cardiac lipid accumulation. SIRT6 gain- or loss-of-function studies showed that SIRT6 downregulated endothelial FA uptake. Mechanistically, SIRT6 suppressed endothelial expression of PPARγ through SIRT6-dependent deacetylation of histone H3 lysine 9 around PPARγ promoter region; and PPARγ reduction mediated SIRT6-dependent inhibition of endothelial FA uptake. Importantly, oral administration of small molecule SIRT6 activator MDL-800 to diabetic mice mitigated cardiac lipid accumulation and diastolic dysfunction.The impairment of endothelial SIRT6 expression links diabetes to HFpEF through the alteration of FA transport across the endothelial barrier. Genetic and pharmacological strategies that restored endothelial SIRT6 function in mice with diabetes alleviated experimental HFpEF by limiting FA uptake and improving cardiac metabolism, thus warranting further clinical evaluation.
Reciprocal cortico-amygdala connections regulate prosocial and selfish choices in mice
Authors: Diego Scheggia, Filippo La Greca, Federica Maltese, Giulia Chiacchierini, Maria Italia, Cinzia Molent, Fabrizio Bernardi, Giulia Coccia, Nicolò Carrano, Elisa Zianni, Fabrizio Gardoni, Monica Di Luca, Francesco Papaleo
Journal: Nature Neuroscience (2022)
Characteristics of JYNNEOS Vaccine Recipients Before and During a Large Multiday LGBTQIA+ Festival — Louisiana, August 9–September 5, 2022
Authors: Rieza H. Soelaeman, Lee Mendoza, Robert McDonald, Julie Hand, Theresa M. Sokol, John T. Brooks, Preetam Cholli, Maribeth Eckert, Braiden Eilers, Jennie J. Gayden, Craig Hayes, Irma Kocer, Sarah M. Labuda, Anna Llewellyn, Scott Santibañez, Colleen Scott, Megan Swanson, Arun Adhikari, Arundhati Bakshi, Samuel Burgess, Javone Davis, Jimmy Gale, Jenna Iberg Johnson, Suryatapa Kar, Kevin Litten, Katherine Murphy, Alyson Neel, Emma Ortega, Gillian Richardson, Sean Simonson, Yanling Zhao
Journal: MMWR Morbidity and Mortality Weekly Report (2022)

monkeypox cases have been identified in the United States (1).Gay, bisexual, and other men who have sex with men (MSM) represent the most affected demographic group in the current multinational outbreak (2).As of October 18, 2022, Louisiana had reported 273 monkeypox cases with 187 (68.5%) among residents of the Louisiana Department of Health (LDH) Southeast Region, which includes the city of New Orleans (3).Southern Decadence is an annual multiday festival in New Orleans catering to persons who are lesbian, gay, bisexual, transgender, queer or questioning, intersex, asexual, and others (LGBTQIA+) that draws 150,000-300,000 participants annually.To prepare for the 2022 festival (September 1-5), LDH requested CDC collaboration for preparedness planning, including statewide pre-event administration of JYNNEOS vaccine to prevent monkeypox.CDC helped acquire 1,500 vials (≤6,000 intradermal doses) of JYNNEOS vaccine through a federal monkeypox large event vaccine pilot in addition to the state's Phase 3 allocation of 4,400 doses.*Concurrently, LDH staff members used multiple strategies to reach out to the LGBTQIA+ community to provide education and increase vaccination coverage among eligible persons, based on local vaccination eligibility criteria (3).Vaccination was available free of charge through public and private health clinics (clinics) beginning in July 2022.† As part of the state's prevention strategy to increase vaccination among eligible Louisiana residents in advance of Southern Decadence, LDH hosted a series of community vaccination events, including large volume events in central locations and smaller, more focused events.The smaller events, organized in collaboration with community partners, were aimed at removing barriers (e.g., stigma and mistrust) and reducing disparities by reaching populations at highest risk, especially
A Health Equity Approach for Implementation of JYNNEOS Vaccination at Large, Community-Based LGBTQIA+ Events — Georgia, August 27–September 5, 2022
Authors: Alexander J. Millman, Damian J. Denson, Michelle L. Allen, John A. Malone, Demetre C. Daskalakis, Diane Durrence, R. Chris Rustin, Kathleen E. Toomey, Tracy Dabbs, Frederick Dobard-Gary, Paige E. Harton, Leah Hoffacker, Huriyyah Lewis, Sheila Lovett, Dewayne Crowder, A Vision, Brittany Johnson, Catherine Monroe, Linda O’Sullivan, Sandra Valenciano, David P. Holland, Joshua O’Neal, Audrey Arona, Dorian Freeman, Alana Sulka
Journal: MMWR Morbidity and Mortality Weekly Report (2022)

Gay, bisexual, and other men who have sex with men (MSM) have been disproportionately affected during the 2022 U.S. monkeypox outbreak, with Black or African American (Black) MSM being the most affected demographic group (1). As of September 28, 2022, Georgia had reported 1,784 monkeypox cases; 98% of which occurred in males and 77% among Black persons (2). As of September 13, 2022, 60% of reported cases were among persons with HIV infection, and 50% of persons with monkeypox had a sexually transmitted infection within the past year (3). Because of racial disparities in the incidence of monkeypox cases and a large proportion of cases among MSM in Georgia, early vaccination beginning in July focused on improving equitable access by establishing new and leveraging existing partnerships with community-based organizations that serve affected populations, including persons with HIV infection. Despite these efforts, disparities persisted because of high demand and limited vaccine supply. The Georgia Department of Public Health (DPH) requested CDC support for a vaccine pilot and received an additional allocation of 5,500 doses of JYNNEOS vaccine for administration at events leading up to and throughout a Black gay Pride festival in Atlanta, a multiday event held Labor Day weekend (September 2-5, 2022). The event celebrates lesbian, gay, bisexual, transgender, queer or questioning, intersex, asexual, and other (LGBTQIA+) communities of color and hosts more than 125,000 attendees each year. Before the festival (as of August 24), 17,546 persons had been vaccinated in Georgia, of whom 96% were male, 34% aged 25-36 years, 44% Black, and 8% Hispanic or Latino (Hispanic) (4).
Reply to Shangqing Ren, Xu Hu, Kai Wang, Qian Lv, and Wang Dong’s Letter to the Editor re: Jihad H. Kaouk, Ethan L. Ferguson, Alp Tuna Beksac, et al. Single-port Robotic Transvesical Partial Prostatectomy for Localized Prostate Cancer: Initial Series and Description of Technique. Eur Urol. 2022;82:551–58
Authors: Ethan L. Ferguson, Jihad H. Kaouk
Journal: European Urology (2022)
Issue Information ‐ TOC
Journal: Hepatology (2022)

HepatologyVolume 76, Issue S1 p. i-ii ISSUE INFORMATIONFree Access Issue Information - TOC First published: 21 October 2022 https://doi.org/10.1002/hep.32701AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume76, IssueS1October 2022Pages i-ii RelatedInformation
Frequency and Underlying Pathology of Pure Vascular Cognitive Impairment
Authors: Shahram Oveisgharan, Robert J. Dawe, Lei Yu, Alifiya Kapasi, Konstantinos Arfanakis, Vladimir Hachinski, Julie A. Schneider, David A. Bennett
Journal: JAMA Neurology (2022)

It is not clear how common pure vascular cognitive impairment (VCI) is in the absence of Alzheimer disease (AD) and/or other neurodegenerative pathologies.To identify participants without AD and other neurodegenerative pathologies and determine the extent to which cerebrovascular disease pathologies were associated with cognitive impairment.This clinical pathological study included participants from 2 ongoing community-based cohorts that began enrollment in 1994 and 1997. Prior to death, participants were observed for a mean (SD) of 8.4 (5.3) years with annual assessments. From 2096 participants who died, 1799 (85.8%) underwent autopsy and 1767 had complete postmortem pathological examination data at the time of data analyses. To identify participants without neurodegenerative pathologies, we categorized them in 3 subgroups. A vascular subgroup was composed of participants without significant levels of neurodegenerative brain pathologies. A neurodegenerative subgroup was composed of participants without significant levels of cerebrovascular disease pathologies. A mixed subgroup was composed of the rest of the participants. Data were analyzed from May 2021 to July 2022.Brain pathology indices obtained by postmortem pathological assessments.The primary outcome was cognitive impairment defined by presence of mild cognitive impairment or dementia. The secondary outcome was cognition assessed by 19 neuropsychological tests.Of 1767 included participants, 1189 (67.3%) were women, and the mean (SD) age at death was 89.4 (6.6) years. In the vascular subgroup (n = 369), cognitive impairment was present in 156 participants (42.3%) and was associated with cerebrovascular disease pathologies (macroinfarcts: odds ratio [OR], 2.05; 95% CI, 1.49-2.82; P < .001; arteriolosclerosis in basal ganglia: OR, 1.35; 95% CI, 1.04-1.76; P = .03) but not AD or other neurodegenerative pathologies, an indication of pure VCI. In mixed-effects models including all the pathologies, only macroinfarcts were associated with a faster cognitive decline rate (estimate, -0.019; SE, 0.005; P < .001) in the vascular subgroup. Further analyses identified macroinfarcts in the frontal white matter to be associated with faster cognitive decline rate when macroinfarcts of cortical and subcortical brain regions were examined in a single model.In this study, pure VCI was not rare. Macroinfarcts, specifically in frontal white matter, were the main cerebrovascular disease pathologies associated with cognitive decline in pure VCI.
Association of Prostate-Specific Antigen Screening Rates With Subsequent Metastatic Prostate Cancer Incidence at US Veterans Health Administration Facilities
Authors: Alex K. Bryant, Kyung Min Lee, Patrick R. Alba, James D. Murphy, Maria Elena Martinez, Loki Natarajan, Michael D. Green, Robert T. Dess, Tori R. Anglin-Foote, Brian Robison, Scott L. DuVall, Julie A. Lynch, Brent S. Rose
Journal: JAMA Oncology (2022)

There is controversy about the benefit of prostate-specific antigen (PSA) screening. Prostate-specific antigen screening rates have decreased since 2008 in the US, and the incidence of metastatic prostate cancer has increased. However, there is no direct epidemiologic evidence of a correlation between population PSA screening rates and subsequent metastatic prostate cancer rates.To assess whether facility-level variation in PSA screening rates is associated with subsequent facility-level metastatic prostate cancer incidence.This retrospective cohort used data for all men aged 40 years or older with an encounter at 128 facilities in the US Veterans Health Administration (VHA) from January 1, 2005, to December 31, 2019.Yearly facility-level PSA screening rates, defined as the proportion of men aged 40 years or older with a PSA test in each year, and long-term nonscreening rates, defined as the proportion of men aged 40 years or older without a PSA test in the prior 3 years, from January 1, 2005, to December 31, 2014.The main outcomes were facility-level yearly counts of incident metastatic prostate cancer diagnoses and age-adjusted yearly metastatic prostate cancer incidence rates (per 100 000 men) 5 years after each PSA screening exposure year.The cohort included 4 678 412 men in 2005 and 5 371 701 men in 2019. Prostate-specific antigen screening rates decreased from 47.2% in 2005 to 37.0% in 2019, and metastatic prostate cancer incidence increased from 5.2 per 100 000 men in 2005 to 7.9 per 100 000 men in 2019. Higher facility-level PSA screening rates were associated with lower metastatic prostate cancer incidence 5 years later (incidence rate ratio [IRR], 0.91 per 10% increase in PSA screening rate; 95% CI, 0.87-0.96; P < .001). Higher long-term nonscreening rates were associated with higher metastatic prostate cancer incidence 5 years later (IRR, 1.11 per 10% increase in long-term nonscreening rate; 95% CI, 1.03-1.19; P = .01).From 2005 to 2019, PSA screening rates decreased in the national VHA system. Facilities with higher PSA screening rates had lower subsequent rates of metastatic prostate cancer. These data may be used to inform shared decision-making about the potential benefits of PSA screening among men who wish to reduce their risk of metastatic prostate cancer.
Oxygen-Saturation Targets for Critically Ill Adults Receiving Mechanical Ventilation
Authors: Matthew W. Semler, Jonathan D. Casey, Bradley D. Lloyd, Pamela G. Hastings, Margaret A. Hays, Joanna L. Stollings, Kevin G. Buell, John H. Brems, Edward T. Qian, Kevin P. Seitz, Li Wang, Christopher J. Lindsell, Robert E. Freundlich, Jonathan P. Wanderer, Jin H. Han, Gordon R. Bernard, Wesley H. Self, Todd W. Rice
Journal: New England Journal of Medicine (2022)

Invasive mechanical ventilation in critically ill adults involves adjusting the fraction of inspired oxygen to maintain arterial oxygen saturation. The oxygen-saturation target that will optimize clinical outcomes in this patient population remains unknown.
Reforming the World Health Organization’s Essential Medicines List
Authors: Thomas J. Hwang, Aaron S. Kesselheim, Kerstin N. Vokinger
Journal: JAMA (2022)

This Viewpoint proposes restructuring the WHO Essential Medicines List to remove consideration of cost and cost-effectiveness from the expert committee reviews of clinical effectiveness, safety, and public health value, and chartering a new framework for pooled global negotiation and procurement of costly medicines included in the list.